bims-agimec Biomed News
on Aging mechanisms
Issue of 2024–10–06
seven papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. Pharmacology of Aging: Drosophila as a Tool to Validate Drug Targets for Healthy Lifespan.
  2. Searching for Beauty and Health: Aging in Women, Nutrition, and the Secret in Telomeres.
  3. Therapeutic approaches to microglial dysfunction in Alzheimer's disease: Enhancing phagocytosis and metabolic regulation.
  4. Pro-inflammatory cytokine 11 plays a pivotal role in inflammaging-associated pathologies.
  5. Cellular stress and epigenetic regulation in adult stem cells.
  6. Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.
  7. Mechanisms of Senescence and Anti-Senescence Strategies in the Skin.
  1. Aging Biol. 2024 Sep 13. 2(1): 20240034
    Pharmacology of Aging: Drosophila as a Tool to Validate Drug Targets for Healthy Lifespan.
    Eliano Dos Santos, Helena M Cochemé.
      Finding effective therapies to manage age-related conditions is an emerging public health challenge. Although disease-targeted treatments are important, a preventive approach focused on aging can be more efficient. Pharmacological targeting of aging-related processes can extend lifespan and improve health in animal models. However, drug development and translation are particularly challenging in geroscience. Preclinical studies have survival as a major endpoint for drug screening, which requires years of research in mammalian models. Shorter-lived invertebrates can be exploited to accelerate this process. In particular, the fruit fly Drosophila melanogaster allows the validation of new drug targets using precise genetic tools and proof-of-concept experiments on drugs impacting conserved aging processes. Screening for clinically approved drugs that act on aging-related targets may further accelerate translation and create new tools for aging research. To date, 31 drugs used in clinical practice have been shown to extend the lifespan of flies. Here, we describe recent advances in the pharmacology of aging, focusing on Drosophila as a tool to repurpose these drugs and study age-related processes.
    DOI:  https://doi.org/10.59368/agingbio.20240034
  2. Nutrients. 2024 Sep 15. pii: 3111. [Epub ahead of print]16(18):
    Searching for Beauty and Health: Aging in Women, Nutrition, and the Secret in Telomeres.
    Virginia Boccardi, Joanna Polom.
      Women typically outlive men, yet they often experience greater frailty and a higher incidence of chronic diseases as they age. By exploring the biological foundations of aging, with a particular focus on telomere dynamics, this manuscript aims to describe how dietary and lifestyle choices can significantly influence the aging process. The review comprehensively examines current research, underscoring the power of nutrition to counteract age-related changes, support healthy aging, and maintain vitality and beauty in women. The exploration of telomeres-the protective caps at the ends of chromosomes-reveals how they serve as markers of cellular aging and are potential targets for interventions aimed at enhancing women's longevity and quality of life. This study also emphasizes the importance of sex-specific approaches and precision medicine in understanding the unique health challenges women face as they age. By proposing targeted strategies, the review seeks to address these challenges, offering insights into preventive measures that can foster resilience, promote well-being, and extend healthy life expectancy in women. Ultimately, this work provides a sophisticated understanding of the aging process in women, highlighting the pivotal role of tailored interventions in preserving both health and beauty.
    Keywords:  aging; beauty; nutrition; sex; telomere; women
    DOI:  https://doi.org/10.3390/nu16183111
  3. Pathol Res Pract. 2024 Sep 25. pii: S0344-0338(24)00525-9. [Epub ahead of print]263 155614
    Therapeutic approaches to microglial dysfunction in Alzheimer's disease: Enhancing phagocytosis and metabolic regulation.
    Waleed Hassan Almalki, Salem Salman Almujri.
      Microglia are essential in neurogenesis, synaptic pruning, and homeostasis. Nevertheless, aging, and cellular senescence may modify their role, causing them to shift from being shields to being players of neurodegeneration. In the aging brain, the population of microglia increases, followed by enhanced activity of genes related to neuroinflammation. This change increases their ability to cause inflammation, resulting in a long-lasting state of inflammation in the brain that harms the condition of neurons. In Alzheimer's Disease (AD), microglia are located inside amyloid plaques and exhibit an inflammatory phenotype characterized by a diminished ability to engulf and remove waste material, worsening the illness's advancement. Genetic polymorphisms in TREM2, APOE, and CD33 highlight the significant impact of microglial dysfunction in AD. This review examines therapeutic approaches that aim to address microglial dysfunction, such as enhancing the microglial capability to engulf and remove amyloid-β clumps and regulating microglial metabolism and mitochondrial activity. Microglial transplanting and reprogramming advancements show the potential to restore their ability to reduce inflammation. Although there has been notable advancement, there are still voids in our knowledge of microglial biology, including their relationships with other brain cells. Further studies should prioritize the improvement of human AD models, establish standardized methods for characterizing microglia, and explore how various factors influence microglial responses. It is essential to tackle these problems to create effective treatment plans that focus on reducing inflammation in the brain and protecting against damage in age-related neurodegenerative illnesses.
    Keywords:  Aging; Alzheimer's; Brain; Microglia; Neurodegeneration
    DOI:  https://doi.org/10.1016/j.prp.2024.155614
  4. Aging Cell. 2024 Oct 03. e14360
    Pro-inflammatory cytokine 11 plays a pivotal role in inflammaging-associated pathologies.
    José M Izquierdo.
      Chronic sterile inflammation contributes to aging-associated pathologies/malignancies like cancer and autoimmune disorders. In their recent Nature article, Widjaja et al. established the pro-inflammatory, pro-fibrotic cytokine 11 (IL11) as a regulatory driver/hub of aging-associated inflammation (inflammaging) in mice. Genetic and pharmacological IL11 blockade reduces inflammaging, improving healthspan, lifespan, and longevity in male and female mice, highlighting IL11 as a new inflammatory aging clock and a potential molecular target in inflammaging-associated human degenerative diseases.
    Keywords:  aging; healthspan; immunotherapy; inflammation; interleukin 11; lifespan; longevity
    DOI:  https://doi.org/10.1111/acel.14360
  5. Life Sci Alliance. 2024 Dec;pii: e202302083. [Epub ahead of print]7(12):
    Cellular stress and epigenetic regulation in adult stem cells.
    Joey Llewellyn, Rithvik Baratam, Luka Culig, Isabel Beerman.
      Stem cells are a unique class of cells that possess the ability to differentiate and self-renew, enabling them to repair and replenish tissues. To protect and maintain the potential of stem cells, the cells and the environment surrounding these cells (stem cell niche) are highly responsive and tightly regulated. However, various stresses can affect the stem cells and their niches. These stresses are both systemic and cellular and can arise from intrinsic or extrinsic factors which would have strong implications on overall aging and certain disease states. Therefore, understanding the breadth of drivers, namely epigenetic alterations, involved in cellular stress is important for the development of interventions aimed at maintaining healthy stem cells and tissue homeostasis. In this review, we summarize published findings of epigenetic responses to replicative, oxidative, mechanical, and inflammatory stress on various types of adult stem cells.
    DOI:  https://doi.org/10.26508/lsa.202302083
  6. Nat Rev Mol Cell Biol. 2024 Oct 03.
    Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.
    Zeming Wu, Jing Qu, Guang-Hui Liu.
      Ageing is a complex biological process in which a gradual decline in physiological fitness increases susceptibility to diseases such as neurodegenerative disorders and cancer. Cellular senescence, a state of irreversible cell-growth arrest accompanied by functional deterioration, has emerged as a pivotal driver of ageing. In this Review, we discuss how heterochromatin loss, telomere attrition and DNA damage contribute to cellular senescence, ageing and age-related diseases by eliciting genome instability, innate immunity and inflammation. We also discuss how emerging therapeutic strategies could restore heterochromatin stability, maintain telomere integrity and boost the DNA repair capacity, and thus counteract cellular senescence and ageing-associated pathologies. Finally, we outline current research challenges and future directions aimed at better comprehending and delaying ageing.
    DOI:  https://doi.org/10.1038/s41580-024-00775-3
  7. Biology (Basel). 2024 Aug 23. pii: 647. [Epub ahead of print]13(9):
    Mechanisms of Senescence and Anti-Senescence Strategies in the Skin.
    Evangelia Konstantinou, Eliane Longange, Gürkan Kaya.
      The skin is the layer of tissue that covers the largest part of the body in vertebrates, and its main function is to act as a protective barrier against external environmental factors, such as microorganisms, ultraviolet light and mechanical damage. Due to its important function, investigating the factors that lead to skin aging and age-related diseases, as well as understanding the biology of this process, is of high importance. Indeed, it has been reported that several external and internal stressors contribute to skin aging, similar to the aging of other tissues. Moreover, during aging, senescent cells accumulate in the skin and express senescence-associated factors, which act in a paracrine manner on neighboring healthy cells and tissues. In this review, we will present the factors that lead to skin aging and cellular senescence, as well as ways to study senescence in vitro and in vivo. We will further discuss the adverse effects of the accumulation of chronic senescent cells and therapeutic agents and tools to selectively target and eliminate them.
    Keywords:  SASP; cellular senescence; p16INK4a; senolytics; senomorphics; senotherapy; skin aging
    DOI:  https://doi.org/10.3390/biology13090647
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